Day: 01/29/2011

Metabolic syndrome common after liver transplant

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Metabolic syndrome is at least twice as common in long-term survivors of liver transplantation as it is in the general public, according to a study scheduled for publication in the January issue of Liver Transplantation.

The researchers saw an association between post-transplant metabolic syndrome (PTMS) and cardiovascular morbidity, but not mortality.

Metabolic abnormalities are “almost universal” after liver transplant, according to senior author Dr. Ziv Ben Ari of the Rabin Medical Center at Beilinson Hospital in Petah Tiqwa, Israel and his colleagues.

They’re not the only ones saying that these days. An article published in the same journal in December 2009 by Pagdala et al called metabolic syndrome after liver transplantation “an epidemic waiting to happen.”

The problem has been attributed as least in part to side effects from immunosuppressant drugs, which include diabetes, high cholesterol, and high triglycerides. In addition, technical improvements in the surgery and in pre- and post-operative care have been allowing liver recipients to grow old.

Today, long-term graft loss and death after liver transplantation are commonly related to age-related complications. According to Dr. Ben Ari and his team, cardiovascular disease is now the main cause of non-graft related mortality in these patients, and particularly in the older individuals.

To analyze their own center’s experience, the researchers looked at medical records for 248 patients who had liver transplantation between 1991 and 2007 at their center and were followed for six months or longer, as well as four patients who received liver transplants elsewhere between 1985 and 1991. Most patients received tacrolimus or cyclosporine, along with mycophenolate mofetil and corticosteroids tapered within 6 months after transplant.

Among the 221 patients for whom pre-transplant data were adequate for assessment, 5.4% had metabolic syndrome. On posttransplant assessments, 51.9% of the 252 patients had metabolic syndrome.

Overall, obesity, hypertriglyceridemia, HDL cholesterol below 40 mg/dL, dyslipidemia, hypertension, and diabetes were all more frequent after transplant.

Patients undergoing transplantation for hepatitis C infection or cryptogenic cirrhosis were significantly more likely to develop post-transplant metabolic syndrome. There was no link between biliary diseases, autoimmune hepatitis, or hepatitis B infection and metabolic syndrome.

While immunosuppression overall wasn’t linked to the development of metabolic syndrome, the researchers did find that use of tacrolimus or cyclosporine predicted posttransplant hypertension and hypertriglyceridemia.

Multivariate analysis identified older age, metabolic derangement, and cryptogenic cirrhosis as independent pre-transplant predictors of metabolic syndrome later on — along with pre-transplant non-alcoholic fatty liver disease and diabetes.

The link between cryptogenic cirrhosis and increased risk could be because many patients may actually have unrecognized non-alcoholic steatohepatitis, Dr. Ben Ari and his team suggest.

Thirteen percent of the patients with post-transplant metabolic syndrome had major vascular events, compared to 5% of patients without it (p=0.027).

Post-transplant metabolic syndrome did not increase the risk of mortality, however (19% of affected patients died during follow-up, compared to 17.3% of patients without metabolic syndrome). Only one death was due to an acute coronary event.

The current findings don’t support a role for immunosuppressant drugs in this condition, the researchers add.

“It is possible that other factors predispose liver transplant recipients” to metabolic syndrome, such as “the return to normal daily life and free food intake, together with normalization of the hypermetabolic state of advanced liver diseases, which can contribute to weight gain…; changes in lipoprotein metabolism induced by the new liver; and the underlying liver disease itself.”

In an editorial, Dr. Sanjaya K. Satapathy and Dr. Michael Charlton of the Mayo Clinic in Rochester, Minnesota, argue that metabolic syndrome that develops after liver transplantation is likely to be modifiable.

“Screening, prevention and treatment strategies, e.g. with nutritional counseling, lipid-lowering therapy, optimal control of hypertension, and choosing immunosuppressants that would (be) less likely to cause (metabolic syndrome) are needed,” they write.

In the meantime, they say, we have an “urgent need for studies of the impact of more aggressive recourse to early diagnosis and sustained implementation of interventions for prevention, diagnosis and treatment” of posttransplant metabolic syndrome.

SOURCE: journal of liver transplant

Obesity Hypoventilation Syndrome

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Piper AJ et al. – Obesity hypoventilation syndrome describes the association between obesity and the development of chronic daytime alveolar hypoventilation. This syndrome arises from a complex interaction between sleep disordered breathing, diminished respiratory drive and obesity–related respiratory impairment, and is associated with significant morbidity and mortality. Therapy directed towards reversing these abnormalities leads to improved daytime breathing, with available treatment options including positive pressure therapy, weight loss and pharmacological management.

Microvascular Angina

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Although low coronary flow reserve (CFR) and microvascular angina (MVA) are associated with poor prognosis, there is initial evidence for reversibility of this abnormal vascular regulation with aggressive medical therapy and control of associated risk factors. Current assessment of MVA is carried out predominantly during cardiac catheterization; however, noninvasive techniques to assess coronary flow reserve are being developed, including PET, MRI, and CT modalities. Quantitative tracer techniques or imaging of metabolic disturbances reflecting ischemia will likely enhance diagnostic approaches for such patients as well as allow more frequent monitoring of response to therapy.

Is Hyperbaric Oxygen Therapy Beneficial in Carbon Monoxide Poisoning?

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HBO therapy did not add benefit to normobaric oxygen therapy in these studies.

In two parallel prospective randomized studies, researchers evaluated the effectiveness of hyperbaric oxygen therapy (HBOT) in patients (age, ≥15 years) with acute isolated carbon monoxide (CO) poisoning who presented to an academic hospital in France between 1989 and 2000. In trial A (mild poisoning), 179 patients with transient loss of consciousness received normobaric oxygen therapy (NBOT) for 6 hours or NBOT for 4 hours plus one session of HBOT. In trial B (severe poisoning), 206 comatose patients (Glasgow Coma Scale score <8) received NBOT for 4 hours plus either one or two HBOT sessions. Each HBOT session lasted 2 hours in a multiplace chamber at 2.0 atmospheres absolute; interval between sessions was 6 to 12 hours. At baseline, 82% of patients in trial A and 65% in trial B had headaches, and 4% and 10%, respectively, had seizures.

At 1 month, patients completed a symptom questionnaire and were evaluated by an intensivist with neurology training who was blinded to treatment group. Complete recovery was defined as absence of patient-reported symptoms and normal physical and neuropsychological exam, “moderate sequelae” was defined as one or more self-reported symptoms, and “severe sequelae” was defined as any objective physical exam finding. In trial A, complete recovery rates were similar in the two groups (approximately 60%), and no patient in either group had severe sequelae. In trial B, complete recovery rates were significantly lower in the group that received two HBOT sessions than in the group that received one session (47% vs. 68%; unadjusted odds ratio, 0.42).

Comment: The trial A findings support the teaching that most patients with mild CO poisoning will improve after removal from the exposure and treatment with high-flow oxygen. The trial B finding is surprising and suggests that HBOT might not benefit even those patients with severe toxicity. Pending a larger trial with clearer toxicity definitions, physicians should contact a regional poison center or HBOT referral center to discuss with consultants the best approach for an individual patient with known CO poisoning, particularly when the treatment might involve transfer of an unstable patient.

— Kristi L. Koenig, MD, FACEP

Published in Journal Watch Emergency Medicine January 28, 2011

Budesonide for Eosinophilic Esophagitis

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Short-term administration of the topical corticosteroid budesonide was highly effective in treating EoE and relieving its symptoms.

Although the prevalence and awareness of eosinophilic esophagitis (EoE) in adults continue to increase, optimal treatment strategies remain undefined. Standard recommended therapy includes systemic or topical steroids (e.g., fluticasone). Recently, the use of budesonide has been reported as highly effective in pediatric patients (JW Gastroenterol Sep 24 2010), but its efficacy in adolescent and adult patients is unknown.

To investigate this issue, researchers randomized 36 patients aged ≥14 years with EoE to receive either 2 mg of budesonide (0.25 mg/mL) suspension or a placebo of saline solution in an industry-supported, double-blind trial. Participants self-administered 4 mL of liquid via nebulizer into the oropharynx, followed by continuous swallowing for 10 minutes, twice daily for 15 days. Proton-pump inhibitors were allowed, but additional types of EoE therapy were discontinued.

Among the budesonide group, esophageal eosinophil load and self-reported dysphagia symptoms decreased from baseline to 15 days (P<0.0001 for both comparisons), as did production of proinflammatory cytokines, cell death, and fibrosis scores. The placebo group experienced no significant changes in these outcomes. Complete histologic remission occurred in 72.2% of the treatment group but in only 11.1% of the placebo group (P<0.0001); among the 13 budesonide-treated patients who achieved remission, endoscopic improvement was evident in the disappearance of almost all white exudates and red furrows identified at baseline. In contrast, corrugated rings persisted in all but one patient. No serious adverse effects occurred; however, 3 of 18 patients in the budesonide group developed clinically asymptomatic esophageal infections with Candida albicans.

Comment: These results suggest that short-term therapy with budesonide leads to a significant improvement in most parameters — even a reduction in fibrosis and fibrosis-related markers. Also, early targeting of the epithelial remodeling might be a key to long-term effectiveness. Specifically, if early anti-inflammatory therapy is effective, perhaps the macroscopic remodeling associated with significant fibrosis (as evident with the corrugated rings) could be prevented. Unfortunately, these data do not address the durability of effect beyond 15 days or the optimal length of therapy. Although the eosinophilic infiltrates respond quickly to this short course of treatment, we do not yet know whether the subepithelial fibrosis would respond better with longer duration of therapy.

— David A. Johnson, MD

Published in Journal Watch Gastroenterology January 28, 2011